Diffuse skin findings secondary to lymph node tularemia in a patient with chronic rheumatoid arthritis on methotrexate.

Tularemia has many atypical presentations which can represent a diagnostic challenge. The history is essential in the investigation of this disease. Bite-induced primary skin lesions should be distinguished from the infrequent immune-mediated secondary skin lesions. Herein, we present an atypical pseudovesicular rash secondary to Francisella tularensis.

Multi-template matching: a versatile tool for object-localization in microscopy images.

BACKGROUND: The localization of objects of interest is a key initial step in most image analysis workflows. For biomedical image data, classical image-segmentation methods like thresholding or edge detection are typically used. While those methods perform well for labelled objects, they are reaching a limit when samples are poorly contrasted with the background, or when only parts of larger structures should be detected. Furthermore, the development of such pipelines requires substantial engineering of analysis workflows and often results in case-specific solutions. Therefore, we propose a new straightforward and generic approach for object-localization by template matching that utilizes multiple template images to improve the detection capacity. RESULTS: We provide a new implementation of template matching that offers higher detection capacity than single template approach, by enabling the detection of multiple template images. To provide an easy-to-use method for the automatic localization of objects of interest in microscopy images, we implemented multi-template matching as a Fiji plugin, a KNIME workflow and a python package. We demonstrate its application for the localization of entire, partial and multiple biological objects in zebrafish and medaka high-content screening datasets. The Fiji plugin can be installed by activating the Multi-Template-Matching and IJ-OpenCV update sites. The KNIME workflow is available on nodepit and KNIME Hub. Source codes and documentations are available on GitHub (https://github.com/multi-template-matching). CONCLUSION: The novel multi-template matching is a simple yet powerful object-localization algorithm, that requires no data-pre-processing or annotation. Our implementation can be used out-of-the-box by non-expert users for any type of 2D-image. It is compatible with a large variety of applications including, for instance, analysis of large-scale datasets originating from automated microscopy, detection and tracking of objects in time-lapse assays, or as a general image-analysis step in any custom processing pipelines. Using different templates corresponding to distinct object categories, the tool can also be used for classification of the detected regions.

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial.

BACKGROUND: There is a high unmet clinical need for treatments of advanced/metastatic biliary tract cancers after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies. PATIENTS AND METHODS: REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase II study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic biliary tract cancer that progressed after gemcitabine/platinum chemotherapy. Patients were randomly assigned 1 : 1 to best supportive care plus either regorafenib 160 mg once daily 3 weeks on/1 week off or placebo until progression or unacceptable toxicity. No crossover was allowed. The primary objective was progression-free survival (PFS). Secondary objectives were response rate, overall survival, and translational analysis. RESULTS: Sixty-six patients with intrahepatic (n = 42), perihilar (n = 6), or extrahepatic (n = 9) cholangiocarcinoma, or gallbladder carcinoma (n = 9) were randomized, 33 to each treatment group (33 per group). At a median follow-up of 24 months, all patients had progressed and six patients were alive. Median treatment duration was 11.0 weeks [95% confidence interval (CI): 6.0-15.9] in the regorafenib group and 6.3 weeks (95% CI: 3.9-7.0) in the placebo group (P = 0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95% CI: 59-90) in the regorafenib group and 34% with placebo (95% CI: 18-51; P = 0.002). Median PFS in the regorafenib group was 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI: 1.2-2.0) in the placebo group (hazard ratio 0.49; 95% CI: 0.29-0.81; P = 0.004) and median overall survival was 5.3 months (95% CI: 2.7-10.5) and 5.1 months (95% CI: 3.0-6.4), respectively (P = 0.28). There were no unexpected/new safety signals. CONCLUSION: Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable biliary tract cancer in the second- or third-line setting. CLINICAL TRIAL REGISTRATION: The trial is registered in the European Clinical Trials Register database (EudraCT 2012-005626-30) and at ClinicalTrials.gov (NCT02162914).

Astonishing Evolution in Oropharyngeal Cancer with Immunotherapy: A Case Report.

Background: Head and neck cancer is particular due to its infiltrative nature and lymphatic extension, with multidisciplinary treatment. Immunotherapy may be a brand-new therapeutic approach.Case Presentation: We report a case of patient with advanced head and neck cancer resistant to cytotoxic treatment, with astonishing response to antibodies anti Programmed Death 1 (PD1).Conclusion: Further studies are needed in order to obtained predictive index of immunotherapy responding, aiming to select appropriately patients for this treatment.

Dendron based antifouling, MRI and magnetic hyperthermia properties of different shaped iron oxide nanoparticles.

Owing to the great potential of iron oxide nanoparticles (NPs) for nanomedicine, large efforts have been made to better control their magnetic properties, especially their magnetic anisotropy to provide NPs able to combine imaging by MRI and therapy by magnetic hyperthermia. In that context, the design of anisotropic NPs appears as a very promising and efficient strategy. Furthermore, their bioactive coating also remains a challenge as it should provide colloidal stability, biocompatibility, furtivity along with good water diffusion for MRI. By taking advantage of our controlled synthesis method of iron oxide NPs with different shapes (cubic, spherical, octopod and nanoplate), we demonstrate here that the dendron coating, shown previously to be very suitable for 10 nm sized iron oxide, also provided very good colloidal, MRI and antifouling properties to the anisotropic shaped NPs. These antifouling properties, demonstrated through several experiments and characterizations, are very promising to achieve specific targeting of disease tissues without affecting healthy organs. On the other hand, the magnetic hyperthermia properties were shown to depend on the saturation magnetization and the ability of NPs to self-align, confirming the need of a balance between crystalline and dipolar magnetic anisotropies.

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.

VSION as high field MRI T1 contrast agent: evidence of their potential as positive contrast agent for magnetic resonance angiography.

Because of their outstanding magnetic properties, iron oxide nanoparticles have already been the subject of numerous studies in the biomedical field, in particular as a negative contrast agent for T2-weighted nuclear magnetic resonance imaging, or as therapeutic agents in hyperthermia experiments. Recent studies have shown that below a given particle size (i.e. 5 nm), iron oxide may be used to provide a significant positive (brightening) effect on T1-weighted MRI. In such an application, not only the size of the crystal, but also the control of the coating process is essential to ensure optimal properties, especially at a very high field (> 3 T). In this work, we focused on the development of very small iron oxide nanoparticles as a potential platform for high field T1 magnetic resonance angiography (MRA) applications. The feasibility has been evaluated in vivo at 9.4 T, demonstrating the usefulness of the developed system for MRA applications.

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI).

Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

Bacteriophage predation promotes serovar diversification in Listeria monocytogenes.

Listeria monocytogenes is a bacterial pathogen classified into distinct serovars (SVs) based on somatic and flagellar antigens. To correlate phenotype with genetic variation, we analyzed the wall teichoic acid (WTA) glycosylation genes of SV 1/2, 3 and 7 strains, which differ in decoration of the ribitol-phosphate backbone with N-acetylglucosamine (GlcNAc) and/or rhamnose. Inactivation of lmo1080 or the dTDP-l-rhamnose biosynthesis genes rmlACBD (lmo1081-1084) resulted in loss of rhamnose, whereas disruption of lmo1079 led to GlcNAc deficiency. We found that all SV 3 and 7 strains actually originate from a SV 1/2 background, as a result of small mutations in WTA rhamnosylation and/or GlcNAcylation genes. Genetic complementation of different SV 3 and 7 isolates using intact alleles fully restored a characteristic SV 1/2 WTA carbohydrate pattern, including antisera reactions and phage adsorption. Intriguingly, phage-resistant L. monocytogenes EGDe (SV 1/2a) isolates featured the same glycosylation gene mutations and were serotyped as SV 3 or 7 respectively. Again, genetic complementation restored both carbohydrate antigens and phage susceptibility. Taken together, our data demonstrate that L. monocytogenes SV 3 and 7 originate from point mutations in glycosylation genes, and we show that phage predation represents a major driving force for serovar diversification and evolution of L. monocytogenes.

On the importance of skewed offspring distributions and background selection in virus population genetics.

Many features of virus populations make them excellent candidates for population genetic study, including a very high rate of mutation, high levels of nucleotide diversity, exceptionally large census population sizes, and frequent positive selection. However, these attributes also mean that special care must be taken in population genetic inference. For example, highly skewed offspring distributions, frequent and severe population bottleneck events associated with infection and compartmentalization, and strong purifying selection all affect the distribution of genetic variation but are often not taken into account. Here, we draw particular attention to multiple-merger coalescent events and background selection, discuss potential misinference associated with these processes, and highlight potential avenues for better incorporating them into future population genetic analyses.

Mycobacterium avium complex disseminated infection in a kidney transplant recipient.

Mycobacterium avium-intracellulare complex (MAC) infections are well known in immunocompromised patients, notably in human immunodeficiency virus infection, but remain scarcely described in kidney transplantation. Moreover, cutaneous involvement in this infection is very unusual. We describe here a disseminated infection caused by MAC in a kidney transplant recipient revealed by cutaneous lesions. This case highlights the need for an exhaustive, iterative microbiologic workup in the context of an atypical disease presentation in a renal transplant patient, regardless of the degree of immunosuppression.

Pulmonary arterial hypertension in adult onset Still's disease: a case report of a severe complication.

BACKGROUND: Adult onset of Still's disease (AOSD) is a rare systemic inflammatory disease. Cardiorespiratory complications are mainly represented by pleural and pericardial disorders and are less frequent than cutaneous and articular complaints. Pulmonary arterial hypertension (PAH) occurring in AOSD is rarely described in literature. CASE PRESENTATION: We present the case of a young patient who developed severe PAH 2 years after diagnosis of AOSD. This is a rare and severe complication which is probably underestimated. CONCLUSIONS: PAH in AOSD can be lethal, and unfortunately its occurrence is unpredictable. Echocardiographic screening of AOSD patients should be evaluated in further trials. Currently, the most suitable treatment is still unknown.

Perceptual attributes for the comparison of head-related transfer functions.

The benefit of using individual head-related transfer functions (HRTFs) in binaural audio is well documented with regards to improving localization precision. However, with the increased use of binaural audio in more complex scene renderings, cognitive studies, and virtual and augmented reality simulations, the perceptual impact of HRTF selection may go beyond simple localization. In this study, the authors develop a list of attributes which qualify the perceived differences between HRTFs, providing a qualitative understanding of the perceptual variance of non-individual binaural renderings. The list of attributes was designed using a Consensus Vocabulary Protocol elicitation method. Participants followed an Individual Vocabulary Protocol elicitation procedure, describing the perceived differences between binaural stimuli based on binauralized extracts of multichannel productions. This was followed by an automated lexical reduction and a series of consensus group meetings during which participants agreed on a list of relevant attributes. Finally, the proposed list of attributes was then evaluated through a listening test, leading to eight valid perceptual attributes for describing the perceptual dimensions affected by HRTF set variations.

Community-acquired infections due to Staphylococcus argenteus lineage isolates harbouring the Panton-Valentine leucocidin, France, 2014.

We describe two cases of human infections caused by Staphylococcus aureus clonal complex (CC) 75, also called Staphylococcus argenteus, harbouring the Panton-Valentine leucocidin (PVL). These two sporadic cases were community-acquired, and identified in France in 2014. Both had an epidemiological link with Mayotte, an overseas department of France located in the Indian Ocean off the south-eastern African coast. This report illustrates that, contrary to previous descriptions, S. argenteus can acquire important virulence factors and be responsible for severe infections.

Gastric Duplication Cyst with Respiratory Epithelium: a Rare Entity.

Gastric duplication cyst is an uncommon entity and management is principally surgical. Diagnosis is often delayed because of the non-specific nature of symptoms. The authors report one case of gastric duplication cyst incidentally diagnosed in a 23-year-old man. He had no specific symptoms but follow up of the unknown retro gastric mass showed an increase in size and cholelithiasis. Magnetic resonance imaging (MRI) was not useful for diagnosis but an endoscopic ultrasound suggested a GIST. The growing size of the mass led to a laparoscopic resection. Histopathology showed a gastric duplication cyst boarded with gastric and respiratory ciliated epithelium. This respiratory differenciation is extremely rare. Our patient is the 25th case reported in the literature. The embryologic origin, diagnosis tools and treatment of those rare cysts are briefly reviewed.

A new magnetic resonance imaging contrast agent loaded into poly(lacide-co-glycolide) nanoparticles for long-term detection of tumors.

The incorporation of a lipophilic Gd chelate (GdDO3A-C12) in biocompatible PLGA poly(D, L-lactide-co-glycolide) nanoparticles was explored as an approach to increase the relaxivity of contrast agents for magnetic resonance imaging. By nanoprecipitation, it was possible to obtain PEGylated gadolinium nanoparticles (mean diameter of 155 nm) with high Gd loading (1.1 × 10(4) Gd centers per nanoparticle). The corresponding GdDO3AC12 ⊂ NPs nanoparticles exhibited an enhanced relaxivity (up to sixfold greater than DOTAREM® at 40 MHz) because the nanoparticle framework constrained the lipophilic Gd chelate motion and favorably impacted the Gd chelate rotational correlation time. T1-weighted imaging at 3 T on phantoms showed enhanced contrast for the GdDO3AC12 ⊂ NPs. Importantly, Gd chelate leakage was almost nonexistent, which suggested that these GdDO3AC12 ⊂ NPs could be useful for long-term MRI detection.

Interface effects and the evolution of ferromagnetism in La2/3Sr1/3MnO3 ultrathin films.

Pulse laser deposited La2/3Sr1/3MnO3 ultrathin films on SrTiO3 substrates were characterized by polar and longitudinal Kerr magneto-optical spectroscopy. Experimental data were confronted with theoretical simulations based on the transfer matrix formalism. An excellent agreement was achieved for a 10.7 nm thick film, while a distinction in the Kerr effect amplitudes was obtained for a 5 nm thick film. This demonstrated the suppression of ferromagnetism due to the layer/substrate interface effects. A revised, depth-sensitive theoretical model with monolayer resolution described the experimental data well, and provided clear cross-section information about the evolution of ferromagnetism inside the film. It was found that the full restoration of the double-exchange mechanism, responsible for the ferromagnetic ordering in La2/3Sr1/3MnO3, occurs within the first nine monolayers of the film. Moreover, all the studied films exhibited magneto-optical properties similar to bulk crystals and thick films. This confirmed a fully developed perovskite structure down to 5 nm.

Extramedullary spinal cysts in dogs.

OBJECTIVE: To (1) synthesize the terminology used to classify extramedullary spinal cysts in dogs to clarify some of the commonly reported misconceptions, and (2) propose a classification scheme to limit confusion with terminology. STUDY DESIGN: Literature review. METHODS: An online bibliographic search was performed in January 2013 for articles relating to extramedullary spinal cysts in dogs using PubMed (http://www.pubmed.gov/) and Google Scholar (http://scholar.google.com/) databases. Only peer-reviewed clinical literature describing cystic lesions pertaining to the spinal cord and associated structures was included. RESULTS: From 1962 to 2013, 42 articles were identified; 25 (95 dogs) reported meningeal cysts, 10 (24 dogs) described 60 extradural cysts, 3 reports (18 dogs) described discal cysts or acute compressive hydrated nucleus pulposus extrusions (HNPE). Spinal cysts were categorized by location based on cross-sectional imaging as meningeal or extradural non-meningeal. Sub-classification was then performed based on surgical findings and pathology. Meningeal cysts included arachnoid diverticulae and Tarlov (perineural) cysts. Extradural non-meningeal cysts included intraspinal cysts of the vertebral joints, ligaments and discs. Discal cysts also fit this category and have been reported extensively in humans but appear rare in dogs. CONCLUSIONS: Extramedullary spinal cysts should be first classified according to location with a sub-classification according to pathologic and surgical findings. Previous canine cases of discal cysts appear to represent a different disease entity and the term acute compressive HNPE is therefore preferred.

Virtual Orientation Tools (VOTj): Fiji plugins for object centering and alignment.

Standardizing image datasets is essential for facilitating overall visual comparisons and enhancing compatibility with image-processing workflows. One way to achieve homogeneity for images containing a single object is to align the object to a common orientation. Here, we propose the Virtual Orientation Tools (VOTj): a set of Fiji plugins to center and align an object of interest in images to a vertical or horizontal orientation. To process an image, the plugin requires either a mask outlining the object or a rough annotation of the object directly drawn by the user in the image. The current object orientation is retrieved using Principal Component Analysis (PCA), from which the optimal alignment is derived. The plugins support multi-dimensional images to allow, e.g., aligning individual time points of a time-lapse. The tools can be used for a variety of samples and imaging modalities. Besides, the plugins enable the interactive alignment of a list of images from a directory for batch execution and can be included in custom image-processing workflows using macro-recording.